Multidrug-Resistant Gram-Negative Bacilli (MDR-GNB)

  Gram-negative bacilli have been a source of healthcare-associated infections for many years and may be found in patients in virtually all healthcare settings as either infection or colonization. In recent years, multidrug-resistant gram-negative organisms have increased in nearly all healthcare settings. Though resistance to any class of antibiotic can occur, it occurs mainly among the extended spectrum beta-lactam antimicrobial agents. This is mainly due to the ability of these organisms to produce extended spectrum beta lactamase enzymes (ESBLs), which make them highly resistant to many of the extended spectrum beta-lactam agents such as the penicillins, cephalosporins, and monobactams. This group includes primarily, Klebsiella, E. coli, P. aeruginosa, and other Enterobacteriaceae, though numerous other drug-resistant gram-negative bacteria strains have also been reported.

 ESBL-producing gram-negative organisms and carbapenemase-producing enterobacteriaceae are a group of emerging infectious pathogens that warrant inclusion in institutional infection control policies. The HICPAC/CDC MDRO 2006 Guidelines recommend contact precautions and other tier 2, intensified control efforts when cases of MDR-GNB are identified. Two of the significant MDR-GNB include:

 1. Acinetobacter baumannii

In recent years, multidrug-resistant A. baumannii (MDRAb) has increased in prominence as a healthcare-associated pathogen. Primarily affecting hospital ICU’s, A. baumannii is associated with longer hospitalizations, greater economic cost, and increased morbidity. Infection due to MDRAb can occur sporadically, but is more commonly associated with outbreaks. MDRAb infections typically manifest as respiratory (ventilator pneumonia), urinary tract, and wound infections (including burn wounds). High rates of bacteremia have also been reported in military service members injured in the Middle East. MDRAb is an ESBL-producing gram-negative bacilli that routinely exhibit resistance to multiple classes or even all classes of antimicrobial drugs leading to greater difficulty in treatment.

A. baumannii is a ubiquitous gram-negative bacillus, found in soil, water, animals, and humans. In the clinical setting, individuals may be infected or colonized and environmental surfaces may be contaminated by A. baumannii where its ability to persist may contribute to transmission between patients, as well as long-term outbreaks. Primarily associated with acute care and long-term acute care facilities, it is now encountered in LTC facilities with increasing frequency. The epidemiology of MDRAb indicates that this is an emerging pathogen and all types of healthcare facilities should be knowledgeable of this pathogen and recommended control measures.

 2. Klebsiella pneumoniae and other Carbapenemase-Producing Enterobacteriaceae

Klebsiella pneumoniae and other gram-negative bacilli have been increasing in clinical importance. While ESBL production among the gram-negative organisms has been an infection control issue for many years, more recently strains of enteric bacilli and other gram-negative organisms have demonstrated production of carbapenemases (beta-lactamase enzymes mediating resistance to the extended spectrum cephosporins as well as carbapenem antibiotics, e.g.,impenem, ertapenem, meropenem).

 In the U.S., a type of carbapenemase referred to as KPC (Klebsiella pneumoniae carbapenemase) has been demonstrated in several species of enteric bacilli but is most commonly found in strains of Klebsiella pneumoniae. A KPC-producing strain of Klebsiella pneumoniae was first reported in North Carolina in 2001 and another was later discovered as part of an outbreak in New York that began in 2000. KPC producing strains have also been reported sporadically from various parts of the U.S., particularly the east coast,  In addition to the high level of resistance commonly found in the KPC-producing strains, the inability of most laboratories to directly detect or confirm the KPC enzyme through routine testing poses additional concern since KPC production may not be detected through standard susceptibility testing.

Methicillin-Resistant Staphylococcus aureus (MRSA)

 Methicillin-resistant S. aureus is a variant of S. aureus which is considered to be resistant to all beta-lactam antibiotics (including penicillins, cephalosporins, and cephamicins). It may also be resistant to one or more other classes of antibiotics. By definition, MRSA must be resistant to one of the following semi-synthetic penicillins: methicillin, oxacillin, or nafcillin. Treatment of MRSA infections should be based on the susceptibility results from the patient culture. MRSA strains have been identified as a major source of healthcare-acquired infections and outbreaks in the U.S. For over four decades, MRSA has presented a challenge for infection control departments of hospitals attempting to control and eradicate this organism. In recent years, long-term acute care hospitals, long-term care facilities, rehabilitation centers, and small community hospitals have seen increasing numbers of cases. These facilities experience continuous reintroduction of resistant organisms due to the recurrent admissions and transfers of patients within these settings.

 More recently, MRSA has also been increasing in the community in individuals without healthcare-associated risk factors. In a 2005 study of S. aureus in Florida outpatient settings, 49.7% of S. aureus isolates were reported to be MRSA (Kolar and Sanderson, 2007). The strains of these CA-MRSA infections are genetically distinct from the typical HA-MRSA commonly encountered in healthcare settings.

1. Healthcare-Associated MRSA (HA-MRSA) – Infection and colonization are typically seen in older individuals with one or more of the risk factors outlined later in this newsletter series. Resistance to multiple classes of antimicrobial agents is common.

 2. Community-Associated MRSA (CA-MRSA) – Community-Associated MRSAc ases are frequently seen in younger persons and involve skin and soft tissue infections. Outbreaks of these infections have been described in numerous populations including people found in correctional facilities (jails and prisons), sport teams, men who have sex with men, commercial fishermen, and minority populations. Resistance to multiple classes of antimicrobials is uncommon. The most common CA-MRSA strain in the United States, the USA300 strain, is routinely resistant to erythromycin. Many of the CA-MRSA infections may be effectively treated with good wound care with or without oral antibiotics, while more resistant strains may require intravenous vancomycin. Frequently, these community-associated cases have initially been misdiagnosed as spider bites. This misdiagnosis prevents timely treatment which may result in a progression of the infection and increased chance of transmission to others. Although genetic variation exists between the types of MRSA, the community-associated variant has been found in healthcare settings and is capable of causing invasive infections and serious complications. HA-MRSA has also been demonstrated in community populations. Since distinction requires laboratory testing, the two variants are most often characterized by their operational definitions.